Back to Search Start Over

Beyond the 5-HT2A Receptor: Classic and Nonclassic Targets in Psychedelic Drug Action.

Authors :
Cameron, Lindsay P.
Benetatos, Joseph
Lewis, Vern
Bonniwell, Emma M.
Jaster, Alaina M.
Moliner, Rafael
Castrén, Eero
McCorvy, John D.
Palner, Mikael
Aguilar-Valles, Argel
Source :
Journal of Neuroscience. 11/8/2023, Vol. 43 Issue 45, p7472-7482. 11p.
Publication Year :
2023

Abstract

Serotonergic psychedelics, such as psilocybin and LSD, have garnered significant attention in recent years for their potential therapeutic effects and unique mechanisms of action. These compounds exert their primary effects through activating serotonin 5-HT2A receptors, found predominantly in cortical regions. By interacting with these receptors, serotonergic psychedelics induce alterations in perception, cognition, and emotions, leading to the characteristic psychedelic experience. One of the most crucial aspects of serotonergic psychedelics is their ability to promote neuroplasticity, the formation of new neural connections, and rewire neuronal networks. This neuroplasticity is believed to underlie their therapeutic potential for various mental health conditions, including depression, anxiety, and substance use disorders. In this mini-review, we will discuss how the 5-HT2A receptor activation is just one facet of the complex mechanisms of action of serotonergic psychedelics. They also interact with other serotonin receptor subtypes, such as 5-HT1A and 5-HT2C receptors, and with neurotrophin receptors (e.g., tropomyosin receptor kinase B). These interactions contribute to the complexity of their effects on perception, mood, and cognition. Moreover, as psychedelic research advances, there is an increasing interest in developing nonhallucinogenic derivatives of these drugs to create safer and more targeted medications for psychiatric disorders by removing the hallucinogenic properties while retaining the potential therapeutic benefits. These nonhallucinogenic derivatives would offer patients therapeutic advantages without the intense psychedelic experience, potentially reducing the risks of adverse reactions. Finally, we discuss the potential of psychedelics as substrates for post-translational modification of proteins as part of their mechanism of action. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
02706474
Volume :
43
Issue :
45
Database :
Academic Search Index
Journal :
Journal of Neuroscience
Publication Type :
Academic Journal
Accession number :
173581378
Full Text :
https://doi.org/10.1523/JNEUROSCI.1384-23.2023